Glucagon is a straight chain peptide hormone consisting of 29 amino acids, which is secreted from a cell of pancreas, and promotes glycogenolysis and gluconeogenesis in the liver. In diabetes patients, secretion and reactivity of glucagon is generally promoted, which is one of the factors causing hyperglycemia. Therefore, a glucagon receptor antagonist can suppress excess glucose production by the liver by blocking the action of glucagon, and is useful as a therapeutic drug for diabetes.
Patent document 1 describes the following compound.
A compound represented by the following formula:
wherein ring A is a benzene ring or a 5- or 6-membered heterocycle, each of which is optionally further substituted;Y is an oxygen atom, a sulfur atom or a nitrogen atom;X is —O—, —S—, —SO—, —SO2—, —CR4R5—O—, —O—OR4R5—, —CO—CR4R5—, —CR4R5CO—, —CR4R5—NR6— or —CO—NR6—;R4 is a hydrogen atom or a C1-6 alkyl group;R5 and R6 are each independently a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C3-10 cycloalkyl group, an optionally substituted C6-14 aryl group, or an optionally substituted 5- or 6-membered heterocyclic group;R1 is an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, an optionally substituted hydroxy group or an acyl group;R2 is a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, an optionally substituted hydroxy group or an acyl group;R3 is —(CH2)3—COOH or —NR7—CR8R9—CR10R11—COOH;R7, R8, R9 and R10 are each independently a hydrogen atom or a C1-6 alkyl group; andR11 is a hydrogen atom, a C1-6 alkyl group or a hydroxy group, provided that when Y is a nitrogen atom, then ring A is not optionally substituted pyrrole, or a salt thereof.
Patent document 2 describes the following compounds.
A compound represented by the following formula:
wherein ring AA is an optionally substituted benzene ring, or an optionally substituted 5- or 6-membered aromatic heterocycle;ring AB is an optionally substituted 5-membered aromatic heterocycle;ring AC is an optionally substituted benzene ring, or an optionally substituted 5- or 6-membered aromatic heterocycle;RA3 is an optionally substituted a C1-6 alkyl group, an optionally substituted C3-10 cycloalkyl group, an optionally substituted C6-14 aryl group or an optionally substituted heterocyclic group;RA4 is a hydrogen atom or a C1-6 alkyl group;RA5 is —(CH2)3—COORA11 or —NRA6—CRA7RA8—CRA9RA10—COORA11;RA6, RA7, RA8, RA9 and RA11 are each independently a hydrogen atom or a C1-6 alkyl group;RA10 is a hydrogen atom, a alkyl group or hydroxy group, or a salt thereof; and
a compound represented by the following formula:
wherein ring A is an optionally substituted benzene ring, or an optionally substituted 5- or 6-membered aromatic heterocycle; ring B is pyrazole;R1 and R2 are each independently an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, an optionally substituted hydroxy group or acyl;R3 is an optionally substituted a C1-6 alkyl group, an optionally substituted C3-10 cycloalkyl group, an optionally substituted C6-14 aryl group or an optionally substituted heterocyclic group;R4 is a hydrogen atom or a C1-6 alkyl group;R5 is —(CH2)3—COOR11 or —NR6—CR7R8—CR9R10—COOR11;R6, R7, R8, R9 and R11 are each independently a hydrogen atom or a C1-6 alkyl group;R10 is a hydrogen atom, a C1-6 alkyl group or a hydroxy group, excluding N-[4-[[(1-phenyl-5-propyl-1H-pyrazol-4-yl)methyl]amino]benzoyl]-β-alanine, or a salt thereof.
Patent document 3 describes the following compounds.    3-{[(6-{[(5-chloro-1-methyl-1H-indol-2-yl)(cyclohexyl)methyl]amino}pyridin-3-yl)carbonyl](methyl)amino}propanoic acid or a salt thereof;    3-{[(6-{[cyclohexyl(5-fluoro-1-methyl-1H-indol-2-yl)methyl]amino}pyridin-3-yl)carbonyl](methyl)amino}propanoic acid or a salt thereof;    3-{[(6-{[(5-chloro-1-methyl-1H-indol-2-yl)(cyclopentyl)methyl]amino}pyridin-3-yl)carbonyl](methyl)amino}propanoic acid or a salt thereof;    3-{[(4-{[(5-chloro-3-methylthieno[2,3-c]pyridin-2-yl)(cyclohexyl)methyl]amino}phenyl)carbonyl](methyl)amino}-propanoic acid or a salt thereof;    3-{[(6-{[(6-chloro-3-methylthieno[3,2-c]pyridin-2-yl)(cyclohexyl)methyl]amino}pyridin-3-yl)carbonyl](methyl)amino}propanoic acid or a salt thereof; and    3-{[(4-{[(6-chloro-3-methylthieno[3,2-c]pyridin-2-yl)(cyclohexyl)methyl]amino}phenyl)carbonyl](methyl)amino}-propanoic acid or a salt thereof.
Patent document 4 describes the following compound.
A compound represented by the following formula:
wherein R1 and R2 are each a hydrogen atom or the like;
X and Y are each CH;
R3 and R4 are bonded to form an optionally substituted 5- to 8-membered ring and the like; and
W is NR5R8 (R5 is a hydrogen atom and the like, and R8 is optionally substituted alkyl and the like), or a salt thereof.
Patent document 5 describes the following compound.
A compound represented by the following formula:
wherein Di is pyrimidine and the like;G is void;G2 is phenyl and the like;G1 is (CR3R3a)uNR3(CR3R3a)w (R3 is a hydrogen atom, R3a is C1-4 alkyl and u+w=0−4); andM is phenyl substituted by -Z-A-B (Z is (CR2R2a)qC(O)(CR2R2a)q1, q+q1=0−2, A is 5-12 heterocycle substituted by R4 (R4 is C(O)R2c,R2c is OH and the like, and B is a hydrogen atom and the like, and the like,or a salt thereof.
Patent document 6 describes the following compound.
A compound represented by the following formula:
wherein R3 is heterocyclocarbonyl optionally substituted bycarboxyl and the like;W is aryl and the like;X is —N(R9)— (R9 is a hydrogen atom);R2 and R8 are each a hydrogen atom, alkyl and the like;A is heteroaryl, —C(O)— or —C(O)NH—;Z is a bond and the like; andR1 is heteroaryl and the like,or a salt thereof.